抗原变异可使得多种致病微生物易于逃避宿主免疫应答。表达在感染红细胞表面的恶性疟原虫红细胞表面蛋白1（PfPMP1）与感染红细胞、内皮细胞、树突状细胞以及胎盘的单个或多个受体作用，在黏附及免疫逃避中起关键的作用。每个单倍体基因组var基因家族编码约60种成员，通过启动转录不同的var基因变异体为抗原变异提供了分子基础。

疟原虫var基因转换速率变化导致抗原变异[英]／Paul H, Robert P, Christodoulou Z, et al//Proc Natl Acad Sci U S A

Responsive polymer materials can adapt to surrounding environments, regulate transport of ions and molecules, change wettability and adhesion of different species on external stimuli, or convert chemical and biochemical signals into optical, electrical, thermal and mechanical signals, and vice versa. These materials are playing an increasingly important part in a diverse range of applications, such as drug delivery, diagnostics, tissue engineering and 'smart' optical systems, as well as biosensors, microelectromechanical systems, coatings and textiles. We review recent advances and challenges in the developments towards applications of stimuli-responsive polymeric materials that are self-assembled from nanostructured building blocks. We also provide a critical outline of emerging developments.

Emerging applications of stimuli-responsive polymer materials

Hydrogels with improved mechanical properties, made by combining polymer networks with ionic and covalent crosslinks, should expand the scope of applications, and may serve as model systems to explore mechanisms of deformation and energy dissipation. Hydrogels are used in flexible contact lenses, as scaffolds for tissue engineering and in drug delivery. Their poor mechanical properties have so far limited the scope of their applications, but new strong and stretchy materials reported here could take hydrogels into uncharted territories. The new system involves a double-network gel, with one network forming ionic crosslinks and the other forming covalent crosslinks. The fracture energy of these materials is very high: they can stretch to beyond 17 times their own length even when containing defects that usually initiate crack formation in hydrogels. The materials' toughness is attributed to crack bridging by the covalent network accompanied by energy dissipation through unzipping of the ionic crosslinks in the second network. Hydrogels are used as scaffolds for tissue engineering1, vehicles for drug delivery2, actuators for optics and fluidics3, and model extracellular matrices for biological studies4. The scope of hydrogel applications, however, is often severely limited by their mechanical behaviour5. Most hydrogels do not exhibit high stretchability; for example, an alginate hydrogel ruptures when stretched to about 1.2 times its original length. Some synthetic elastic hydrogels6,7 have achieved stretches in the range 10–20, but these values are markedly reduced in samples containing notches. Most hydrogels are brittle, with fracture energies of about 10 J m−2 (ref. 8), as compared with ∼1,000 J m−2 for cartilage9 and ∼10,000 J m−2 for natural rubbers10. Intense efforts are devoted to synthesizing hydrogels with improved mechanical properties11,12,13,14,15,16,17,18; certain synthetic gels have reached fracture energies of 100–1,000 J m−2 (refs 11, 14, 17). Here we report the synthesis of hydrogels from polymers forming ionically and covalently crosslinked networks. Although such gels contain ∼90% water, they can be stretched beyond 20 times their initial length, and have fracture energies of ∼9,000 J m−2. Even for samples containing notches, a stretch of 17 is demonstrated. We attribute the gels’ toughness to the synergy of two mechanisms: crack bridging by the network of covalent crosslinks, and hysteresis by unzipping the network of ionic crosslinks. Furthermore, the network of covalent crosslinks preserves the memory of the initial state, so that much of the large deformation is removed on unloading. The unzipped ionic crosslinks cause internal damage, which heals by re-zipping. These gels may serve as model systems to explore mechanisms of deformation and energy dissipation, and expand the scope of hydrogel applications.

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Highly stretchable and tough hydrogels

基礎講座 電気泳動(Electrophoresis)

The widespread use of controlled molecular-level motion in key natural processes suggests that great rewards could come from bridging the gap between the present generation of synthetic molecular systems, which by and large rely upon electronic and chemical effects to carry out their functions, and the machines of the macroscopic world, which utilize the synchronized movements of smaller parts to perform specific tasks. This is a scientific area of great contemporary interest and extraordinary recent growth, yet the notion of molecular-level machines dates back to a time when the ideas surrounding the statistical nature of matter and the laws of thermodynamics were first being formulated. Here we outline the exciting successes in taming molecular-level movement thus far, the underlying principles that all experimental designs must follow, and the early progress made towards utilizing synthetic molecular structures to perform tasks using mechanical motion. We also highlight some of the issues and challenges that still need to be overcome.

Synthetic molecular motors and mechanical machines.

The trend towards miniaturization in optical imaging, diagnostics and lab-on-a-chip technology is creating a demand for sophisticated microlenses. A new type of smart liquid microlens has been developed that differs from most current devices in that it is self-focusing. The key component is a stimuli-responsive hydrogel integrated into a microfluidic system and acting as a container for a liquid droplet. The hydrogel simultaneously senses stimuli and actuates a change in droplet shape — and hence focal length. Stimuli can include biological and chemical agents and physical parameters. At this micrometre scale, pinned liquid-liquid interfaces are used to attain stable devices, and response times of ten to a few tens of seconds. Lenses can have virtually any focal length and are readily integrated into arrays. Despite its compactness, the human eye can easily focus on different distances by adjusting the shape of its lens with the help of ciliary muscles1. In contrast, traditional man-made optical systems achieve focusing by physical displacement of the lenses used. But in recent years, advances in miniaturization technology have led to optical systems that no longer require complicated mechanical systems to tune and adjust optical performance. These systems have found wide use in photonics, displays and biomedical systems. They are either based on arrays of microlenses with fixed focal lengths2,3,4,5, or use external control to adjust the microlens focal length6,7,8,9,10,11,12. An intriguing example is the tunable liquid lens, where electrowetting or external pressure manipulates the shape of a liquid droplet and thereby adjusts its optical properties. Here we demonstrate a liquid lens system that allows for autonomous focusing. The central component is a stimuli-responsive hydrogel13 integrated into a microfluidic system and serving as the container for a liquid droplet, with the hydrogel simultaneously sensing the presence of stimuli and actuating adjustments to the shape—and hence focal length—of the droplet. By working at the micrometre scale where ionic diffusion and surface tension scale favourably14, we can use pinned liquid–liquid interfaces to obtain stable devices and realize response times of ten to a few tens of seconds. The microlenses, which can have a focal length ranging from -∞ to +∞ (divergent and convergent), are also readily integrated into arrays that may find use in applications such as sensing, medical diagnostics and lab-on-a-chip technologies15,16,17,18,19.

Adaptive liquid microlenses activated by stimuli-responsive hydrogels

Electrovibration is the tactile sensation of an alternating potential between the human body and a smooth conducting surface when the skin slides over the surface and where the current is too small to stimulate sensory nerves directly. It has been proposed as a high-density tactile display method, for example to display pictographic information to persons who are blind. Previous models for the electrovibration transduction mechanism are based on a parallel-plate capacitor in which the electrostatic force is insensitive to polarity. We present experimental data showing that electrovibratory perceptual sensitivity to positive pulses is less than that for negative or biphasic pulses and propose that this disparity may be due to the asymmetric electrical properties of human skin. We furthermore propose using negative pulses for insulated tactile displays based on electrovibration because their sensory thresholds were found to be more stable than for waveforms incorporating positive pulses

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Polarity Effect in Electrovibration for Tactile Display

Programmable autonomous micromixers and micropumps have been designed and realized via a merger between MEMS and microfluidic tectonics (/spl mu/FT). Advantages leveraged from both fabrication platforms allow for relatively simple and rapid fabrication of these microfluidic components. Nickel (Ni) microstructures, driven by an external rotating magnetic field, are patterned in situ and serve as the microactuators in the devices. /spl mu/FT permits in situ patterning through the use of a step-and-repeat fabrication process known as liquid-phase photopolymerization (LP/sup 3/). LP/sup 3/ is a polymer-based fabrication process tool that offers additional fabrication materials, including responsive hydrogels that expand and contract under different stimuli. Using pH- and temperature-sensitive hydrogels as clutches, autonomous micromixers and micropumps have been fabricated and tested that perform as closed-loop microsystems. The step-and-repeat fabrication process allows pre-programming of the system, like a programmable read-only memory chip, to be sensitive to a desired stimulus. Different Ni blade designs, and pH-sensitive hydrogel geometries and dimensions have been designed and tested to better ascertain their effects on micromixing efficiency and response times of hydrogels (related to the autonomous functionality), respectively. Temperature-responsive hydrogels have allowed for development of temperature-sensitive micromixers and micropumps with applications in areas demanding temperature control. [1498].

/pdf/programmable-autonomous-micromixers-and-micropumps-1s3upt1orv.pdf

Programmable autonomous micromixers and micropumps

Traditional optical systems utilize mechanical parts (e.g., gears, motors, and drivers) to allow adjustable focusing and magnification. Emerging variable-focus microlenses have exhibited the potential to miniaturize and advance optical systems without the need for mechanical parts, impacting significantly on a multitude of fields, such as cameras, biomedical instruments, and lab-on-a-chip systems. A variety of variable-focus liquid microlenses have been demonstrated based on different mechanisms, including reorientation of liquid crystals, electrowetting of a liquid droplet, and mechanical actuation of polymeric materials. These microlens technologies rely on external controls and power supplies; for example, additional electric fields are necessary to drive both electrowetting liquid microlenses and liquid-crystal microlenses, and external actuation devices are required to control the pressure in flexible polymer microlenses. The requirement for additional discrete components increases the complexity and makes integration, especially in lab-on-a-chip applications, challenging. We are interested in taking advantage of smart materials to realize variable-focus liquid microlenses without requiring external controls and power supplies. Responsive hydrogels are smart materials that undergo significant and reversible volume change in response to environmental stimuli by absorbing and releasing water through the network interstitials of the hydrogels. The ability to convert chemical energy directly into mechanical work means that the hydrogels can function as sensors, actuators, and power sources in specific conditions (e.g., the human body) where most external controls and power supplies are limited or difficult to obtain. By taking advantage of responsive hydrogels, we previously reported an innovative approach for realizing smart-liquid microlenses responsive to environmental changes. The liquid microlens extends the concept of pinned liquid/liquid interfaces to apertures to form a liquid microlens. A hydrogel ring located within a microfluidic channel responds to an environmental change by expanding and contracting, which regulates the shape of a water/oil interface (i.e., a liquid microlens), thus, tuning the focal length of the microlens. In this paper, we demonstrate thermoresponsive variable-focus cylindrical microlenses and spherical microlens arrays formed using liquid/liquid interfaces. Thermoresponsive reversible N-isopropylacrylamide (NIPAAm) hydrogels were employed; unconstrained NIPAAm hydrogels swell by as much as a factor of ten when the temperature decreases from above to below the hydrogel’s lower critical solution temperature (LCST). First, arbitrary shapes of microlenses (e.g., cylindrical and spherical) can be realized by patterning apertures that have corresponding shapes (e.g., rectangular and circular, respectively). This benefits the implementation of various microlenses with different shapes, among which variable-focus cylindrical lenses are of strong interest for a multitude of optical applications such as stretching an image, focusing light into a slit, and correcting low-order aberration. Second, we extended single variable-focus spherical microlenses to microlens arrays, allowing the devices not only to have wide-angle observation and parallel optical signal acquisition, but also to implement combinatorial interrogation of complicated environments in microfluidics by individually regulating the focal lengths of the microlens elements. In a typical variable-focus cylindrical microlens (Fig. 1a), a rectangular window was photopatterned in a 250 lm thick polymer slip to form an aperture. The sidewall of the aperture was treated to be hydrophilic (water contact angle of 29°) through an oxygen plasma treatment; the top-side surface of the aperture was rendered hydrophobic (water contact angle of 118°) by coating it with an octadecyltrichlorosilane solution. Thus, a hydrophobic/hydrophilic contact line coincided at the boundary between the sidewall and top-side surface of the aperture. A thermoresponsive NIPAAm hydrogel (LCST = 32 °C) ring was photopatterned in a 750 lm deep microfluidic channel. When the hydrogel ring was filled with deionized water through the aperture, a water meniscus emerged from the rectangular aperture, and the peripheral boundary of the meniscus was pinned stably at the hydrophobic/hydrophilic contact line. Mineral oil was stored within a C O M M U N IC A IO N

/pdf/variable-focus-liquid-microlenses-and-microlens-arrays-3ea4w913su.pdf

Abhishek K. Agarwal

Papers

Adaptive liquid microlenses activated by stimuli-responsive hydrogels

Polarity Effect in Electrovibration for Tactile Display

Programmable autonomous micromixers and micropumps

Variable-focus liquid microlenses and microlens arrays actuated by thermoresponsive hydrogels

A point-of-care PCR test for HIV-1 detection in resource-limited settings